Spiro systems construction

Both malonyl-CoA and methylmalonyl-CoA are then utilized as extender units. The heterocyclic rings are easily accounted for the spiro system is merely a ketal, though the tetrahydrofu-ran ring requires further hydroxylations of the basic skeleton for its construction. Avermectins are usually isolated as a mixture in which the main a component has a 2-methylpropyl group... 

Construction of the required spiro system was performed through a modified Pomeranz-Fritsch sequence (see Scheme 25.1). The nitrogen function had to be acetylated before cyclization with formation of ring B could be carried out. The sodium borohydride reduction to furnish ochrobirine proceeded with a high degree of specificity. 

A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

Details are given of the successful construction of a novel reversible system of network polymers between bifunctional monomers by utilising the equilibrium polymerisation system of a spiro orthoester. Molecular structures were determined by NMR and IR spectroscopy. 9 refs. 

Studies directed toward the synthesis of bicyclomycin have resulted in the discovery of efficient routes to the construction of the 2-oxa-8,10-diazabicyclo[4.2.2]decane system (160). Thus, the monolactim ether (155) with a hydroxypropyl side chain at position 3, on oxidation with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ), gave the product (156) in good yield, presumably via an iminium species (Scheme 51). No trace of the spiro compound (157) could be detected in this reaction. The formation of (156) is probably kinetically controlled. Prior protection of the alcohol as a silyl ether, followed by DDQ oxidation, gave the pyrazinone (158) subsequent deprotection and acid treatment gave the thermodynamically preferred spiro compound (159). The method has been extended to the synthesis of (160), having an exocyclic methylene this compound is a key intermediate in the total synthesis of bicyclomycin [88JCS(P1)2585]. 

Efficient, highly enantioselective construction of quaternary stereocenter on P-keto esters under phase-transfer conditions has been achieved using N-spiro chiral quaternary ammonium bromide lh as catalyst [32]. This system has a broad generality in terms of the structure of P-keto esters 65 and alkyl halides (Scheme 5.31). 

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

The MCI cyclopentene annulations proceed with moderate efficiency and have been utilized for the construction of polycyclic molecules with fused, spiro and tethered ring systems (e.g. equations 118-120)28. With bis(phenyliodonium) diyne salts, biscyclopentene annulations are observed (e.g. equation 121)86. 

The vinylbenzothiazoles can also function as very efficient Michael acceptors (78TL13). The a-lithio derivative of acetone dimethylhydrazone undergoes clean conjugate addition to the vinylbenzothiazole derived from cyclohexanone to provide, upon quenching the a-lithiobenzothiazole anion with methyl iodide and hydrolyzing the dimethylhydrazone group, the ketone (579) (93% overall, 86 14 cis trans). The pure cis keto benzothiazole was converted to the cis keto aldehyde (580), and then cyclized with p-toluenesulfonic acid to the A -3-octalone (581 Scheme 127). Many other examples of the use of this chemistry for the construction of fused and spiro ring systems have been developed. 

Ring systems containing cyclohexadienones spiro-linked to a cyclic ether can be constructed by oxidative C—O bond connection in the intramolecular mode. Five-membered ring formation is well documented, and the reactions may be efficient. For example, the linked bisnaphthols (230), (231) and (232)... 

More interesting reactions are possible when the carbonyl-alkene cyclizations are applied in a tandem reaction sequence [4b]. The three precursor motifs of spiro , separated , and fused ring systems 22, 24 and 26, respectively, were each constructed however, not all cyclized readily (Scheme 6). In each reaction the intermediate alkene bearing the EWG, which both receives the radical and transfers the radical in the last cyclization, was activated for addition from the <9-stannyl ketyl. With the appropriate placement of the alkene tether in the starting substrate, complex ring structures can be synthesized in a one-pot procedure. 

In contrast to the above, 4n systems arc spiro-antiaromatic. This is easily shown by constructing the diagram (Figure 12.13) for spiro-nonatctraenc. Compared to... 

Ethoxyallylidenetriphenylphosphorane (94) has been shown to be a novel cyclohexanone annelating reagent, undergoing addition to a/8-unsaturated ketones to produce 2-alkoxycyclohexa-1,3-dienes (masked cyclohexenones and useful eno-philes) (Scheme 24)7 The method is highly versatile, permitting the construction of monocyclic, fused, bicyclic, and spiro-ring systems. 

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